(R)-2-(N-(4-(3,6,9,12-tetraoxapentadec-14-yn-1-yloxy)benzyl)-4-methoxyphenylmethoxyphenylsulfonamido)-3-methylbutanoic acid | 1378928-89-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-2-(N-(4-(3,6,9,12-tetraoxapentadec-14-yn-1-yloxy)benzyl)-4-methoxyphenylmethoxyphenylsulfonamido)-3-methylbutanoic acid
• 英文别名: (2R)-2-[(4-methoxyphenyl)sulfonyl-[[4-[2-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethoxy]ethoxy]phenyl]methyl]amino]-3-methylbutanoic acid
• CAS: 1378928-89-2
• 化学式: C₃₀H₄₁NO₁₀S
• 分子量: 607.722
• InChiKey: KAQUZYNPRVKHGF-GDLZYMKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  42
• 可旋转键数：
  22
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  138
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (R)-2-(N-(4-(3,6,9,12-tetraoxapentadec-14-yn-1-yloxy)benzyl)-4-methoxyphenylmethoxyphenylsulfonamido)-3-methylbutanoic acid 在 N-甲基吗啉 、 盐酸 、 copper(ll) sulfate pentahydrate 、 1-羟基苯并三唑 、 sodium ascorbate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 (R)-2-(N-(4-((1-(1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl)-2,5,8,11-tetraoxatridecan-13-yl)oxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide
  参考文献：
  名称：

  A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation

  摘要：

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.

  DOI：

  10.1021/jm300199g
• 作为产物：
  描述：

  丙炔基-四甘醇-甲磺酸酯 在 盐酸 、 sodium tetrahydroborate 、 potassium carbonate 、 caesium carbonate 、 lithium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.5h， 生成 (R)-2-(N-(4-(3,6,9,12-tetraoxapentadec-14-yn-1-yloxy)benzyl)-4-methoxyphenylmethoxyphenylsulfonamido)-3-methylbutanoic acid
  参考文献：
  名称：

  A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation

  摘要：

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.

  DOI：

  10.1021/jm300199g

文献信息

• A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation
  作者：Verena Hugenberg、Hans-Jörg Breyholz、Burkhard Riemann、Sven Hermann、Otmar Schober、Michael Schäfers、Umesh Gangadharmath、Vani Mocharla、Hartmuth Kolb、Joseph Walsh、Wei Zhang、Klaus Kopka、Stefan Wagner

  DOI：10.1021/jm300199g

  日期：2012.5.24

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.